It is known that demineralized bone matrix induces new bone formation when implanted in the soft tissue by a process generally designated as matrix induced bone formation (see Urist, M. R., Science, 150: 893-899 (1965)). There have been numerous efforts to extract and identify the active material (or materials) which induces this process, and it has been generally referred to in the literature as bone morphogenetic protein(s) (BMP). It is uncertain whether BMP is a single material or a mixture of materials, and there does not appear to be agreement among the investigators as to which material, if any, is the bone morphogenetic protein.
The therapeutic use of BMP offers considerable advantages over use of traditional bone graft materials. While not intended to be limited by any theory, one hypothesis assumes that BMP transforms tissue cells into osteoblasts (cells that manufacture bone). During a process that replicates normal human fetal development, BMP-induced osteoblasts form cartilage which, over a period of several months, evolve into solid bone. Thus BMP may be useful for replacing bone that has been destroyed by disease or accident, for use in treatment of scoliosis victims, for treatment of mal- or mis-formed bone, for use in healing of a fracture, etc.
It is thus an object of the present invention to produce a functional bone calcification factor or a component thereof, which is a 22 KD protein identified by its entire amino acid sequence, which initiates calcification.
It is another object of the present invention to produce this biologically active 22 KD protein by recombinant DNA technology.
It is yet another object of the present invention to construct nucleic acid screening probes for isolation of the gene comprising the 22 KD BCF.
It is yet another object of the present invention to provide an amino acid sequence of mature 22 KD BCF which can be thus prepared by direct biochemical synthesis or from constituent amino acids by peptide synthesis, for example as by the Merrifield method, and particularly by use of automated peptide synthesis technology.
These and other objects of the invention will be apparent from the following description of the preferred embodiments and from practice of the invention.